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Investigation Of The Localisation, Transport And Vaccine Potential Of Group A Streptococcal Cell Surface Proteins.
Funder
National Health and Medical Research Council
Funding Amount
$505,523.00
Summary
Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis. Additionally, serious sequeale, including rheumatic fever and acute glomerulonephritis, may result following repeated infection. We have recently examined the GAS cell wall and identified 23 proteins that are surface exposed, 20 of which are novel. We hypothesise that a number of these surface exposed proteins represe ....Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis. Additionally, serious sequeale, including rheumatic fever and acute glomerulonephritis, may result following repeated infection. We have recently examined the GAS cell wall and identified 23 proteins that are surface exposed, 20 of which are novel. We hypothesise that a number of these surface exposed proteins represent candidate vaccine antigens capable of conferring protective immunity. We therefore propose to examine these surface proteins as components of experimental vaccines against GAS.Read moreRead less
Estimating The Burden Of Group A Streptococcal Diseases In Victoria
Funder
National Health and Medical Research Council
Funding Amount
$386,760.00
Summary
Despite the considerable advances in the diagnosis and treatment of group A streptococcal (GAS) diseases made during the last century, the impressive spectrum of infections caused by this organism continues to have a significant impact in developed countries. This spectrum includes diseases that are mild but common (e.g. sore throat, skin sores), rare but very severe (e.g. bloodstream infections, flesh-eating bacteria) and those that are more common in developing countries and the Aboriginal pop ....Despite the considerable advances in the diagnosis and treatment of group A streptococcal (GAS) diseases made during the last century, the impressive spectrum of infections caused by this organism continues to have a significant impact in developed countries. This spectrum includes diseases that are mild but common (e.g. sore throat, skin sores), rare but very severe (e.g. bloodstream infections, flesh-eating bacteria) and those that are more common in developing countries and the Aboriginal population (e.g. rheumatic fever, kidney disease). Streptococcal sore throat remains one of the most common childhood infections, and severe group A streptococcal diseases are thought to be increasing in incidence in Australia. Yet, there are no accurate data on the incidence and costs of these or other GAS diseases in non-Aboriginal Australians, or in most other populations around the world. It is becoming more urgent to collect this data as numerous vaccine candidates are entering human trials, new approaches to the treatment of sore throat are emerging, and new strategies to treat and control the spread of severe disease are being developed. We propose a comprehensive strategy to measure the incidence, prevalence and costs of each group of GAS diseases. We will follow a group of families for 12 months to detect cases of GAS sore throat and skin sores and measure the impact on the family. We will survey children in schools to estimate the prevalence of skin sores. We will check hospital records to calculate the number of cases of rheumatic fever and kidney disease. And we will maintain surveillance for severe diseases by checking hospital and laboratory records. We will also check to see if family members of people with severe disease have the GAS bacterium in their throats. We will then compile these data into a comprehensive estimate of the burden of disease in Victoria, and estimate the cost-effectiveness of different treatment and prevention strategies.Read moreRead less
Molecular Mechanisms Of Macrophage-mediated Renal Injury.
Funder
National Health and Medical Research Council
Funding Amount
$59,756.00
Summary
The complete loss of kidney function means that survival of the patient is dependent upon lifelong dialysis or a kidney transplant. Dialysis patients have a poor quality of life, and the provision of dialysis and transplantation treatments are very costly. Our current therapies reply upon steroids and cytotoxic drugs. These therapies have only limited efficacy and are associated with significant side-effects. Therefore, we need to develop new and specific approaches to the treatment of kidney di ....The complete loss of kidney function means that survival of the patient is dependent upon lifelong dialysis or a kidney transplant. Dialysis patients have a poor quality of life, and the provision of dialysis and transplantation treatments are very costly. Our current therapies reply upon steroids and cytotoxic drugs. These therapies have only limited efficacy and are associated with significant side-effects. Therefore, we need to develop new and specific approaches to the treatment of kidney disease. To do this, we need to begin by understanding the way in which the kidney is damaged in disease. Our studies have shown that white blood cells, called macrophages, enter the kidney in large numbers during disease. Indeed, the greater the number of macrophages within the kidney, the more severe the kidney injury. We believe, one the basis of animal studies, that these macrophages cause kidney injury. However, we do not know the mechanisms by which this happens. To address this question, we have developed a rat model of kidney disease in which we can take macrophages, which we have cultured in the laboratory, and inject them into animals and they will enter the kidney and cause injury. This allows us to modify specific macrophage functions in culture and then determine whether this affects the ability of these macrophages to cause kidney injury in the animal. In this way, we will be able to understand the mechanisms by which macrophages cause kidney injury. We hope that these studies will enable us to develop new and specific approaches to the treatment of human kidney disease.Read moreRead less
Many different diseases can cause chronic kidney failure. Mast cell participation in most of these is prominent. These cells traditionally regarded as important only in allergy are now known to be capable of inducing injury in many other situations. The availability of safe drugs to block mast cell function makes determination of the role of mast cells in chronic kidney diseases important.
Closing The Gap: Implementing Effective Treatments To Improve Post-operative Nausea And Vomiting
Funder
National Health and Medical Research Council
Funding Amount
$175,303.00
Summary
Nausea and vomiting are common after surgery, concern 80% people undergoing surgery, and are managed by drugs with unwanted side effects. High quality evidence supports acupuncture being a safe and effective non-drug therapy for this complaint. This study will examine if and how acupuncture can be delivered by doctors and nurses around operation time. In future, people may have the choice of using acupuncture or drugs, or both, for preventing or treating nausea and vomiting after surgery.
Interaction Of Group A Streptococci With Intracellular Innate Immune Defence
Funder
National Health and Medical Research Council
Funding Amount
$824,252.00
Summary
The pathogenic bacterium group A streptococcus (GAS) is estimated to cause ~700 million cases of self-limited throat or skin infection each year worldwide. GAS infections result in over 600,000 human deaths. This disease burden places GAS in the “top 10” causes of human infectious disease deaths worldwide. We have discovered a hitherto unknown mechanism by which GAS subvert the human immune system. An improved understanding of this mechanism will lead to novel ways to combat GAS infections.
Worldwide Molecular Analysis Of Streptococcus Pyogenes Scarlet Fever Outbreaks
Funder
National Health and Medical Research Council
Funding Amount
$544,041.00
Summary
The microorganism group A Streptococcus (also called GAS or Streptococcus pyogenes) ranks among the top 10 infectious disease killers of humans. Recently, outbreaks of scarlet fever have occurred in both Asia and the United Kingdom, placing a serious strain on health systems. The reasons underlying these outbreaks remain unknown. Our team will lead the global effort to characterise this rise in scarlet fever, and provide recommendations and solutions to health professionals.
Blood Group Antigen Recognition By Group A Streptococcus Mediates Host Colonisation
Funder
National Health and Medical Research Council
Funding Amount
$470,821.00
Summary
Group A streptococcus (GAS) is responsible for approximately 700 million cases of localised infection and 600,000 cases of invasive infection globally each year. Certain bacteria have been shown to recognise sugars (known as glycans) on host cells. This project will look at how GAS use sugars at the surface of host cells to initiate disease, and determine if differences in the types of sugars present on host cells alter the ability of GAS to initiate infection.